Review article: Recommendations for detection, assessment and management of suspected drug-induced liver injury during clinical trials in oncology patients.

BACKGROUND: Drug-induced liver injury (DILI) is a major concern for oncology drugs in clinical practice and under development. Monitoring cancer patients for hepatotoxicity is challenging as these patients may have abnormal liver tests pre-treatment or on-study for many reasons including liver injury due to past oncology treatments, hepatic metastases, medical co-morbidities such as heart failure, and concomitant medications. At present, there are no regulatory guidelines or position papers that systematically address best practices pertaining to DILI detection, assessment and management in oncology patients. AIMS: The goals of this review are (1) to examine and interpret the available evidence and (2) to make recommendations for detection, monitoring, adjudication, and management of suspected hepatocellular DILI during oncology clinical trials. METHODS: This manuscript was developed by the IQ Consortium (International Consortium for Innovation and Quality in pharmaceutical development) DILI Initiative that consists of members from 17 pharmaceutical companies, in collaboration with academic and regulatory DILI experts. The manuscript is based on extensive literature review, expert interpretation of the literature, and several rounds of consensus discussions. RESULTS: This review highlights recommendations for patient eligibility for clinical trials with or without primary/metastatic liver involvement, as well as changes in liver tests that should trigger increased monitoring and/or discontinuation of study drug. Guidance regarding causality assessment for suspected DILI events, rechallenge and dose-modification is provided. CONCLUSIONS: This review brings together evidence-based recommendations and expert opinion to provide the first dedicated consensus for best practices in detection, assessment, and management of DILI in oncology clinical trials.

Drug-Induced Liver Injury in the Elderly: Consensus Statements and Recommendations from the IQ-DILI Initiative.

The elderly demographic is the fastest-growing segment of the world's population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) that encourage data collection in the elderly and recommend improved practices that will facilitate a more inclusive approach. To establish what is already known about DILI in the elderly and pinpoint key gaps of knowledge in this arena, a working definition of "elderly" is required that accounts for both chronologic and biologic ages and varying states of frailty. In addition, it is critical to characterize the biological role of aging on liver function, as well as the different epidemiological factors such as polypharmacy and inappropriate prescribing that are common practices. While data may not show that elderly people are more susceptible to DILI, DILI due to specific drugs might be more common in this population. Improved characterization of DILI in the elderly may enhance diagnostic and prognostic capabilities and improve the way in which liver safety is monitored during clinical trials. This summary of the published literature provides a framework to understand and evaluate the risk of DILI in the elderly. Consensus statements and recommendations can help to optimize medical care and catalyze collaborations between academic clinicians, drug manufacturers, and regulatory scientists to enable the generation of high-quality research data relevant to the elderly population.

Liver biopsy for assessment of suspected drug-induced liver injury in metabolic dysfunction-associated steatohepatitis clinical trials: Expert consensus from the Liver Forum.

BACKGROUND: Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. AIM: To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. METHODS: From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. RESULTS: Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. CONCLUSIONS: Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.

The predictive value of liver tests for the presence of liver metastases.

Aim: To analyze the predictive value of biochemical liver tests in patients with malignant melanoma, breast, colorectal or lung cancers at the time of diagnosis of liver metastases. Methods: A retrospective review of patients with the above-mentioned solid tumors at MedStar Georgetown University Hospital from 2016-2020. Results: The highest optimal cutoff according to sensitivity and specificity for the presence of liver metastases was for AST ≥1.5 × ULN for melanoma, lung, and breast cancers and ≥2 × ULN for colorectal cancer, ALT ≥1.25 × ULN for melanoma, breast and colorectal cancers and ≥1.5 × ULN for lung cancer, and ALP ≥1.5 × ULN for melanoma, breast and colorectal cancers. Conclusion: Using thresholds of liver enzymes above the ULN may improve the diagnostic accuracy for the presence of liver metastases.

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology.

Monitoring for liver injury remains an important aspect of drug safety assessment, including for oncotherapeutics. When present, drug-induced liver injury may limit the use or result in the discontinuation of these agents. Drug-induced liver injury can exhibit with a wide spectrum of clinical and biochemical manifestations, ranging from transient asymptomatic elevations in aminotransferases (TAEAT) to acute liver failure. Numerous oncotherapeutics have been associated with TAEAT, with published reports indicating a phenomenon in which patients may be asymptomatic without overt liver injury despite the presence of grade ≥3 aminotransferase elevations. In this review, we discuss the occurrence of TAEAT in the context of oncology clinical trials and clinical practice, as well as the clinical relevance of this phenomenon as an adverse event in response to oncotherapeutics and the related cellular and molecular mechanisms that may underlie its occurrence. We also identify several gaps in knowledge relevant to the diagnosis and the management of TAEAT in patients receiving oncotherapeutics, and identify areas warranting further study to enable the future development of consensus guidelines to support clinical decision-making.

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study.

BACKGROUND: There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. METHODS: We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. RESULTS: There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1-8.4). CONCLUSIONS: This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors.

BACKGROUND: Pexidartinib is approved in the U.S. for tenosynovial giant cell tumors (TGCTs). Herein, we assessed the hepatic safety profile of pexidartinib across patients with TGCTs receiving pexidartinib. MATERIALS, AND METHODS: Hepatic adverse reactions (ARs) were assessed by type and magnitude of liver test abnormalities, classified as (a) isolated aminotransferase elevations (alanine [ALT] or aspartate [AST], without significant alkaline phosphatase [ALP] or bilirubin elevations), or (b) mixed or cholestatic hepatotoxicity (increase in ALP with or without ALT/AST and bilirubin elevations, based on adjudication). Median follow-up from initial pexidartinib treatment was 39 months (range, 32-82) in 140 patients with TGCTs across clinical studies NCT01004861, NCT02371369, NCT02734433, and NCT03291288. RESULTS: In total, 95% of patients with TGCTs (133/140) treated with pexidartinib (median duration of exposure, 19 months [range, 1-76]), experienced a hepatic AR. A total of 128 patients (91%) had reversible, low-grade dose-dependent isolated AST/ALT elevations without significant ALP elevations. Five patients (4%) experienced serious mixed or cholestatic injury. No case met Hy's law criteria. Onset of hepatic ARs was predominantly in the first 2 months. All five serious hepatic AR cases recovered 1-7 months following pexidartinib discontinuation. Five patients from the non-TGCT population (N = 658) experienced serious hepatic ARs, two irreversible cases. CONCLUSION: This pooled analysis provides information to help form the basis for the treating physician's risk assessment for patients with TCGTs, a locally aggressive but typically nonmetastatic tumor. In particular, long-term treatment with pexidartinib has a predictable effect on hepatic aminotransferases and unpredictable risk of serious cholestatic or mixed liver injury. IMPLICATIONS FOR PRACTICE: This is the first long-term pooled analysis to report on the long-term hepatic safety of pexidartinib in patients with tenosynovial giant cell tumors associated with severe morbidity or functional limitations and not amenable to improvement with surgery. These findings extend beyond what has been previously published, describing the observed instances of hepatic toxicity following pexidartinib treatment across the clinical development program. This information is highly relevant for medical oncologists and orthopedic oncologists and provides guidance for its proper use for appropriate patients within the Pexidartinib Risk Evaluation and Mitigation Safety program.

Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.

Onapristone Extended Release: Safety Evaluation from Phase I-II Studies with an Emphasis on Hepatotoxicity.

INTRODUCTION: Antiprogestins have demonstrated promising activity against breast and gynecological cancers, but liver-related safety concerns limited the advancement of this therapeutic class. Onapristone is a full progesterone receptor antagonist originally developed as an oral contraceptive and later evaluated in phase II studies for metastatic breast cancer. Because of liver enzyme elevations identified during clinical studies, further development was halted. Evaluation of antiprogestin pharmacology and pharmacokinetic data suggested that liver enzyme elevations might be related to off-target or metabolic effects associated with clinical drug exposure. OBJECTIVE: We explored whether the use of a pharmaceutic strategy targeting efficacious systemic dose concentrations, but with diminished peak serum concentrations and/or total drug exposure would mitigate hepatotoxicity. Twice-daily dosing of an extended-release formulation of onapristone was developed and clinically evaluated in light of renewed interest in antiprogestin therapy for treating progesterone receptor-positive breast and gynecologic cancers. The hepatotoxic potential of extended-release onapristone was assessed from two phase I-II studies involving patients with breast, ovarian, endometrial, and prostate cancer. RESULTS: Among the 88 patients in two phase I-II studies in progesterone receptor-positive malignancies treated with extended-release onapristone, elevated alanine aminotransferase/aspartate aminotransferase levels were found in 20% of patients with liver metastases compared with 6.3% without metastases. Of five patients with grade 3 or higher alanine aminotransferase elevations with or without bilirubin elevations (four with breast cancer and one with endometrial cancer), four were assessed as unrelated to extended-release onapristone by the safety data review committee. Furthermore, while the fifth patient's liver enzyme elevations were considered possibly drug related by the study investigator, they were adjudicated as unlikely to be related (< 25% likelihood) by a subsequent independent hepatologist. CONCLUSIONS: These results suggest that the extended-release formulation by reducing drug exposure may be associated with a reduced risk of hepatotoxicity, and supports the continued clinical evaluation of extended-release onapristone for treating progesterone receptor-positive cancers.

Significant Variation in the Detection Rates of Proximal Serrated Polyps Among Academic Gastroenterologists, Community Gastroenterologists, and Colorectal Surgeons in a Single Tertiary Care Center.

INTRODUCTION: Recent studies have demonstrated that the protective effect of colonoscopy against colorectal cancer is lower in the proximal colon. Proximal serrated polyps, including sessile serrated adenomas and proximal hyperplastic polyps, can be frequently missed and pose a risk of interval cancers. AIM: To investigate the overall adenoma detection rate (ADR) and the proximal serrated polyp detection rate (PSPDR) among academic gastroenterologists, community gastroenterologists, and colorectal surgeons from a single institution, all of whom have received formal training in colonoscopy during their fellowship. METHODS: All complete screening colonoscopies for patients aged 50 or older with a good to excellent bowel preparation performed by different endoscopists at Medstar Washington Hospital Center (Washington, DC) from July 2015 to December 2017 were reviewed. Pathology reports of the resected polyps were manually reviewed. RESULTS: A total of 2850 screening colonoscopies meeting the inclusion criteria were performed by 18 endoscopists (6 academic, 7 community, and 5 colorectal surgeons). There was no significant difference in the mean ADR among the three groups of endoscopists: academic gastroenterologists, community gastroenterologists, and colorectal surgeons (40.3% vs 36.0% vs 39.6%, respectively). However, academic gastroenterologists had a significantly higher PSPDR compared to community gastroenterologists or colorectal surgeons (12.3% vs 5.4% vs 4.5%, respectively, ANOVA p = 0.006). CONCLUSION: Our novel data show that academic gastroenterologists had a significantly higher PSPDR compared to community gastroenterologists or colorectal surgeons despite a comparable overall ADR among the three groups. PSPDR may be considered as an important quality indicator for colonoscopy, apart from ADR.

Hepatotoxicity induced by immune checkpoint inhibitors: a comprehensive review including current and alternative management strategies.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) block cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) receptors that control antitumor activities of lymphocytes. While highly efficacious, these drugs have been associated with several immune-related adverse events (irAEs) due to the disruption of self-tolerance. Immune-mediated hepatitis (IMH) usually presents as mild elevations of liver enzymes though it can rarely be associated with life-threatening hepatic injury. Areas covered: A comprehensive review was performed to define the clinicopathologic forms of liver injury associated with ICIs, comparing the various ICI classes as well as comparing this form of IMH with idiopathic autoimmune hepatitis and drug-induced autoimmune hepatitis. Liver biopsy has proven very useful in selected patients. A specific form of fibrin ring granulomatous hepatitis appears to be associated with IMH. The current societal treatment algorithms and emerging data were reviewed to determine when to utilize corticosteroids. Expert opinion: Monitoring for severe ICI-IMH is recommended although acute liver failure remains rare. Most patients with grade 3-4 hepatotoxicity respond to corticosteroids, but a subset of patients with mild hepatitis on liver biopsy resolve without steroids and need to be carefully selected in concert with the consultation of a hepatologist.

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.

While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for leflunomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

Sumatriptan-associated ischemic colitis: case report and review of the literature and FAERS.

BACKGROUND AND AIMS: Ischemic colitis (IC) is being increasingly recognized, although specific etiological causes are observed in a minority of patients. While several drugs have been associated with IC, most remain anecdotal reports. We recently treated a patient with IC thought to be related to sumatriptan for migraines, and performed a literature review along with a review of the FDA Adverse Event Reporting System (FAERS) database to identify additional cases. METHODS: A MEDLINE/PubMed literature review was conducted using standard IC search terms to identify published cases of sumatriptan and other related "triptan" drug causes of IC. In addition, through a Freedom of Information Act request, we reviewed the adverse gastrointestinal events linked to sumatriptan contained in the FAERS database for the 5-year period 12 March 2008-11 March 2013, in order to determine whether unpublished cases might exist. Our case of IC was analyzed using a causality assessment tool initially developed for use in cases of alosetron (a 5-HT3 receptor antagonist)-related IC. RESULTS: Five published reports (containing a total of seven patients) describing sumatriptan-associated IC in the English language literature were found and reviewed. Another four published reports of related 5-HT1 receptor agonists causing IC (razitriptan n = 1 and naratriptan n = 3) were also analyzed. Among spontaneous reports of possible IC contained in the FAERS database for sumatriptan, there were 19 adverse events coded as "ischemic colitis" and another six coded as "intestinal ischemia" over a 5-year period ending March 2013, but clinical details were lacking. Similarly, five reports of possible IC from FAERS were mentioned in an earlier published report from the late 1990s. All of the published case reports of sumatriptan and related drugs were deemed to have the classic clinical findings and all recovered. There was one instance of possible recurrent IC symptoms in one patient re-exposed to sumatriptan, but not in another. We found that the IC scoring system developed for alosetron was applicable in our sumatriptan case. CONCLUSIONS: Among drug-related causes of IC, sumatriptan joins a growing list of agents with literature reports supported by the finding of suspected cases of IC in the FAERS database. However, the true incidence of IC due to sumatriptan, as well as other causes, cannot be accurately determined because of the likelihood of under-reporting. The structured IC scoring system appears to be applicable for drug-related as well as other etiological causes of IC.

Polypharmacy and comorbidity are associated with a lower early virologic response in hepatitis C patients treated with first generation protease inhibitor triple therapy: a preliminary analysis.

BACKGROUND AND AIMS: The protease inhibitors (PIs) boceprevir and telaprevir are currently standard treatment as part of triple therapy regimens (TTx) for chronic HCV genotype 1 (GT1) patients. In this preliminary analysis, we have compared demographic variables, polypharmacy, and Charlson's comorbid index (CCI) with Rapid Virological Response (RVR) and extended RVR (eRVR) rates in HCV GT1 patients receiving PI containing TTx. METHODS: Retrospective descriptive cohort study. RESULTS: Among 74 HCV patients (46 M, 28 F; age: 54.43 ± 9.52 years; African Americans: 59.5 %) in this initial analysis, 44 % achieved RVR. All these RVR patients also achieved eRVR. Patients achieving RVR and eRVR were 50 ± 11.7 (mean ± SD) years old, compared to 58 ± 5.2 years without an RVR (p < 0.005). The average number of medications taken by patients achieving RVR and eRVR was 5 ± 2.7 compared to 9.24 ± 3.4 in patients not achieving RVR and eRVR (p < 0.005). Twenty-five percent of patients who were not on CYP3A4 inhibitors had an RVR and eRVR compared to 63.2 % who were taking CYP3A4 inhibitors (p = 0.001). Patients achieving RVR and eRVR had a lower CCI (1.61 ± 1.37) compared to those not achieving RVR and eRVR (2.8 ± 2.7; p = 0.02). Multivariate analysis also revealed a significant correlation between increased polypharmacy and CCI with lower RVR and eRVR rates. CONCLUSIONS: These preliminary treatment data demonstrate that increased polypharmacy and higher degrees of comorbidity decrease RVR and eRVR rates among patients receiving first generation PI-containing TTx regimens.

Drug-induced liver injury in the elderly.

Historically, the elderly have been considered to be at increased risk for drug-induced liver injury (DILI). Animal studies have demonstrated changes in hepatic physiology that affect drug metabolism in the aging liver; however, there is no evidence that this leads to any appreciable deterioration of liver function in healthy older humans. Updated data from international DILI registries give us pause to consider whether the elderly are truly at increased risk to develop hepatic injury. Instead, hepatotoxicity in the elderly appears to be more a function of drug exposure, polypharmacy and drug-drug interactions. Isoniazid and benoxaprofen are the only two agents with a well-studied correlation between increasing age and risk of DILI. Nevertheless, given the increasing proportion of patients over age 65 in the U.S. and abroad, the influence of age on the risk of DILI is the focus of this review.

Dermatologists' awareness of and screening practices for hepatitis B virus infection before initiating tumor necrosis factor-α inhibitor therapy.

OBJECTIVE: The aim of the study was to assess dermatologists' awareness of available guidelines and drug package insert information on the screening for and management of hepatitis B (HBV) infection in patients receiving tumor necrosis factor-α inhibitor (TNF-αI) drug therapies for dermatological disorders. MATERIALS AND METHODS: An electronic descriptive cross-sectional questionnaire was administered to a random, nationwide sample of physician members of the American Academy of Dermatology. Each participating physician answered 8 questions regarding his or her awareness of the risk of HBV reactivation. RESULTS: More than half of the dermatologists surveyed (52%) were aware of guidelines regarding TNF-αI use in dermatological disorders. Dermatologists who were aware of the guidelines performed universal screening 81% of the time versus 3% of those who were unaware. Approximately 30% of the dermatologists were aware of drug manufacturers' package insert warnings for risk of HBV reactivation with TNF-αIs. Screening in their high-risk patients was highly variable because >90% performed screening in patients with a history of hepatitis or with elevated liver-associated enzymes. Most (73%) screened appropriately with HB surface antigen. One case of HBV reactivation was observed with infliximab use for psoriasis treatment. CONCLUSIONS: Based on this survey, improving education among dermatologists regarding the risks of HBV reactivation and its prevention for patients receiving TNF-αI seems warranted. More specific consensus guidelines are recommended to achieve universal screening as the standard of care in these patients.

The safety of same-day endoscopy and percutaneous liver biopsy.

BACKGROUND AND AIMS: The aim of this study was to review our experience with same-day endoscopy (SDE) plus percutaneous liver biopsy (PLB) and to evaluate its safety compared to PLB alone. METHODS: We retrospectively examined records of all patients who underwent PLB between January 2003 and September 2009 and identified those who underwent SDE and matched these patients to those undergoing PLB alone. Serious adverse events (SAEs) were analyzed using our endoscopic database (EndoPro, Pentax) and were divided into those occurring immediately post-procedure and those occurring after discharge. RESULTS: In the study, 479 patients underwent 507 PLBs and 52 patients (11%) were identified as having SDE. No statistical differences were apparent in terms of sex, age, baseline laboratory values, medical comorbidities, cirrhosis, or liver lesions. The most common indication for PLB was chronic hepatitis C (HCV). A total of 15 patients underwent upper endoscopy (EGD); 37 patients underwent colonoscopy (most for colorectal cancer screening). One (1.9%) SAE occurred in the SDE and PLB group. This patient experienced microperforation of the hepatic flexure secondary to abnormal anatomy and underwent immediate laparoscopic repair with an unremarkable post-op course. Four (0.88%) SAEs occurred with PLB alone, mostly prolonged pain from subcapsular hematoma, with no transfusions or surgery required. CONCLUSIONS: At our institution, SDE with PLB is often performed and appears to be a safe method of practice. We believe that performance of EGD or colonoscopy on the same day as PLB optimizes medical resources and results in patient satisfaction without sacrificing safety.